Surgical Research


Theme 1: ‘ClOsed Negative-pressure Therapy After ColorecTal Surgery a multicenter randomized controlled trial (CONTACT)’

Prof. dr. J.F. Lange, REPAIR-research group, Department of Surgery

Surgical site infection (SSI) following abdominal surgery is considered one of the most significant and frequent complications resulting in mortality, morbidity, and costs. Through time, surgeons have explored different interventions to decrease the SSI rate, such as pre-operative antibiotic prophylaxis and aseptic techniques. Negative pressure wound therapy (NPWT) was reported for the first time in 1997, as a novel technique, which brought a revolution in treating chronic and other difficult-to-manage wounds. Usage of NPWT is now a widely accepted therapy for secondarily healing wounds and nowadays the application of NPWT to surgical incision healing by primary intention is a subject undergoing intense study in different disciplines.

More than two decades after its introduction, laparoscopic approach has become the standard of care for colorectal surgery. The feasibility and advantages of laparoscopic approach have been well documented. Despite all prophylactic interventions and sterility measures, (preoperative antibiotic use and aseptic operative technique) SSI rates following laparoscopic colorectal surgery remain high and vary from 4% to 16.7%. Given the significant patient morbidity associated with this complication, closed incision followed by NPWT is a non-widely used but promising new technique, urgently requiring further investigation.

The aim of the current study is to evaluate effectiveness of a negative pressure wound therapy device and herewith measure SSI rate for closed incisional wounds. The secondary objective is to evaluate quality of life, post-operative complications, cost-effectiveness, and cosmesis.

The research master student will be part of the REPAIR-research group (Research Projects for Abdominal surgery Innovation Rotterdam) and will extensively participate in the trial.This study offers the experience of coordinating and participating in a multicenter randomized controlled trial, as well as collecting and interpreting data. At the end of the research project a scientific article will be written by the student and submitted to a peer-reviewed medical journal.

Theme 2: Effect of Music on the Clinical outcome after Hip fracture OPeratIoNs (MCHOPIN): a multicenter randomized controlled trial

Prof. dr. J. Jeekel, REPAIR-research group, Department of Surgery, Prof. dr. M.H.J. Verhofstad, Trauma Research Unit, Department of Surgery, Prof. dr. J.F. Lange, REPAIR-research group, Department of Surgery

Proximal femur fractures are the most common fractures in the elderly. These elderly patients, often with significant comorbidity and polypharmacy, are at high risk for delirium, which increases the risk of other postoperative complications, a longer hospital stay and a reduced functional outcome. Recent systematic reviews and meta-analysis have shown a significant beneficial effect of perioperative music on postoperative pain and anxiety.
Also, several studies have shown a reduced need for intraoperative sedative medication, as well as a reduction in postoperative analgesic medication requirement, when perioperative music as a non-pharmacological intervention was used. This study will investigate the effect of perioperative music on the clinical outcome in proximal femur fracture patients.

The main objective of this study is to investigate whether music as an intervention is effective in reducing the occurrence of postoperative delirium in proximal femur fracture surgery patients. Secondary objectives are the effects of perioperative music on pain, anxiety, medication use, postoperative complications, neurohormonal stress response, hospital length of stay, nursing home length of stay, 30-day mortality, 90-day readmission, 90-day functional ability to perform daily living activities and costs. The intervention group will receive pre-operative, intraoperative and postoperative music as an intervention, the control group will not receive the music intervention. All patients will wear headphones before and during surgery. Patients in the intervention group can choose music from a preselected playlist.

This national, multicenter randomized controlled trial will include 690 proximal femur fracture surgery patients. The research master student will extensively participate in the trial, which involves a wide range of specialists like (trauma)surgeons, anaesthesiologists and geriatricians, and will play a role in coordinating the trial, collecting and interpreting data, and potential authorship of a scientific article to be submitted to a peer-reviewed medical journal.

Theme 3: Intraoperative Music to PROMote PaTient oUtcome (IMPROMPTU): a double-blinded, placebo-controlled randomized controlled trial

Prof. dr. J. Jeekel, REPAIR-research group, Department of Surgery, Dr. B.P.L. Wijnhoven, gastrointestinal surgeon, Department of Surgery, Prof. dr. J.F. Lange, REPAIR-research group, Department of Surgery

Perioperative music has a significant beneficial effect on postoperative pain and anxiety, possibly through attenuation of the stress response to surgery. Several studies have shown that auditory sensory information is still processed by the brain even under deep sedation. This study will investigate the effect of intraoperative music under general anaesthesia in upper gastrointestinal cancer surgery patients.

The main objective of this study is to investigate whether intraoperative music reduces postoperative pain in upper gastrointestinal cancer surgery patients. Secondary objectives are the effects of intraoperative music on intraoperative medication requirement, postoperative opioid requirement, stress response to surgery, intraoperative vital parameters, postoperative complications, hospital length of stay and 30-day mortality. Patients will be randomly allocated to one of two study arms. All participants will wear headphones during surgery. The intervention group will receive intraoperative music as an intervention; the control group will not hear music. The music intervention will consist of a preselected playlist of music based on recommendations of literature and experts.

The research master student will extensively participate in the trial, and will play a role in patient inclusion, collecting and interpreting data, and potential authorship of a scientific article to be submitted to a peer-reviewed medical journal.

Theme 4: ‘Predicting Functional Outcomes of Rectal Cancer Surgery Using Video

Prof. Dr. J. F. Lange, REPAIR-research group, Department of Surgery.

Rectal cancer is diagnosed in roughly a fifth of new cases regarding malignancies of the alimentary tract. After establishing the diagnosis, a patient will usually undergo neo-adjuvant therapy (in the form of radiotherapy, if not combined with chemotherapy). After this, according to the current guideline, the afflicted segment of rectum will be surgically removed by applying the Total Mesorectal Excision principle (TME). The past years, using this technique in the majority of the cases, survival rates of about 65% and 55%, for five and ten years after the initial diagnosis respectively, were reported. What these number do not reflect is the manner in which the Quality of Life of these patients is affected. The fact is that a large number of patients cope with postoperative functional disorders which are directly linked to the surgical procedure, i.e. difficulty urinating or urinary incontinence, obstipation or fecal incontinence, loss of libido, impotence in males or dyspareunia in females. Moreover, these problems occur frequently: 30% to 70% of patients suffer from bladder dysfunction, 40% to 60% experience obstipation or fecal incontinence, and up to 80% of males and 60% of females report any form of sexual dysfunction.

To evaluate which surgical actions and factors during the surgical treatment for rectal cancer specifically affect postoperative urological, genital and rectal function, we aim to prospectively employ video analysis in patients undergoing surgical resection for rectal cancer. To determine postoperative dysfunction, participating patients will be asked to complete questionnaires regarding pelvic organ function on separate occasions.

The Research Master-student will participate in all aspects of a clinical trial, including involvement in the establishment and coordination of the trial, writing the study protocol and acquiring medical ethical committee approval, and composing the patient questionnaires. During the trial he or she will recruit participating centers, visit surgeries of participating patients, contact study patients, and perform data collection and interpretation. After the trial, at least one article will be written by the student and submitted to a peer-reviewed medical journal and presented at medical conferences.

Theme 5: Component seperation techniques for the closure of complex abdominal hernias, TAR versus Ramirez

Prof. dr. J.F. Lange, REPAIR-research group, Department of Surgery

Incisional hernias are one of the most frequent complications after abdominal surgery and remain an important surgical challenge. The reoperation rate after hernia repair remains high and may exceed over 30%. In patients presenting with complex or giant abdominal wall hernias with significant loss of domain, it is not possible to obtain (tension free) closure with conventional techniques.

To close complex abdominal wall hernias component separation techniques have gained popularity. Two main component separation techniques are available, the anterior component separation (Ramirez) and transvers abdominis release (TAR). Both techniques aim to achieve additional lateralization of the posterior and anterior rectus sheath, to facilitate closure relatively free of strain.

Component separation techniques are relatively rare interventions and are therefore challenging to study. To date both the Ramirez and TAR techniques have only been studied in single armed cohort studies. Therefore, the aim of the current study is to retrospectively compare both techniques for early postoperative complication (surgical site occurrences), hernia recurrence after two years and reoperations rates in a two armed multicenter study.

The research master student will be part of the REPAIR-research group (Research Projects for Abdominal surgery Innovation Rotterdam). The student will design and coordinate the study, including the collection and interpretation of data. At the end of the research project a scientific article will be written by the student and submitted to a peer-reviewed medical journal.

Theme 6: ‘Searching for the ideal stitch tension to obtain optimal wound closure’

Prof. dr. J.F. Lange, REPAIR-research group, Department of Surgery

Midline laparotomy is the most common used technique to enter the abdominal cavity in abdominal surgery. Unfortunately, this technique is associated with several surgical site occurrences such as wound dehiscence, surgical site infections, and incisional hernia. These complications are partially associated with the suturing technique. A high suture tension may incise through tissue, potentially leading to ischemia, edema and necrosis. However, a too low suture tension can result in wound dehiscence. An ideal tension in each stitch is required in order to perform wound closure correctly. To date, a tension measuring device is in development.

The aim of the current study is to validate this devise and measure the tension associated with different techniques to close the abdomen in an experimental setting. The force tensor will be studied in a mechanical abdominal wall model (the AbdoMan), in an experimental animal model or in a postmortem human body.

The research master student will be part of the REPAIR-research group (Research Projects for Abdominal surgery Innovation Rotterdam) and will extensively participate in the trial.

The student will be coordinating the trial, collecting and interpreting data. At the end of the research project a scientific article will be written by the student and submitted to a peer-reviewed medical journal.

Theme 7: Hepato-pancreato-biliary- and Transplant surgery

The division of HPB- and Transplant Surgery of Erasmus MC offers the NIHES Research Master-students a broad range of research opportunities within a stimulating clinical and academic environment. The Erasmus MC HPB/Transplant group focuses on surgery of liver and pancreas, as well as liver and kidney transplantation. The team has been part of many new developments in both oncologic and transplantation surgery. The student will be supported by supervisors with a wide experience in randomized clinical trials (e.g. in the field of pancreatic cancer surgery and kidney transplantation) as well as epidemiologic and experimental study designs (e.g. registry studies, machine perfusion for donor organs). Under supervision of the project leader, the student will be actively involved in protocol optimalisation, data collection, analysis and interpretation of results, leading to a scientific paper as a first author and submitted to a peer-reviewed medical journal. The team offers ample opportunities to participate, network and improve his/her professional skills. Participation and presentation of research work on international meetings is encouraged.

Subtheme 1: The impact of aorto-iliac stenosis on patient and graft survival in kidney transplant recipients

Project leader: R.C. Minnee

Project description: The constantly increasing number of aorto-iliac lesions in patients with end-stage renal disease seems to be a result of three main factors: increased recipient age, frequent atherosclerosis accompanying with end-stage renal disease and commonly present metabolic syndrome. These arterial calcifications of the aorta and iliac vessels are a relative contra-indication for kidney transplantation due to cardiovascular comorbidity. The influence of aorto-iliac vascular disease on graft survival, surgical complexity and surgical complications remains poorly explored. There is no international consensus which patients with aorto-iliac calcifications can be safely transplanted and which patients have higher risk on graft loss or surgical complications. Our two key objectives are: (I) to evaluate patient survival after kidney transplantation in patients with aorto-iliac calcifications, (II) to analyze and compare the cost-effectiveness of kidney transplantation in patients with aorto-iliac calcifications and dialysis.

Subtheme 2: Pre-emptive kidney transplantation with cadaveric donors including extended criteria grafts

Project leader: H. Hartog

Project description: Pre-emptive kidney transplantation is considered the optimal treatment securing superior graft and patient survival compared to other renal replacement therapy options and transplantation after inception of dialysis. However, our knowledge of pre-emptive kidney transplantation is predominantly based on data of pre-emptive live donor kidney transplantation. Cadaveric grafts, especially extended criteria (ECD) grafts, are increasingly used for pre-emptive transplant candidates but may not confer a similar transplant benefit, since residual kidney function allows time to delay transplantation and wait for a better graft. The objective of this registry study is to determine the actual benefit of pre-emptive kidney transplantation using cadaveric donors, including ECD grafts. Data will be requested from the Eurotransplant and NHS-BT registry databases.

Subtheme 3: Prehabilitation to enhance postoperative recovery after live kidney donation

Project leader: R.C. Minnee

Project description: Kidney donors are healthy individuals who donate their kidney to patients with end-stage renal disease. Fatigue after kidney donation is a common complaint that affects the quality of life after kidney donation and delayed return to daily practice. A recent systematic review shows that the quality of life only returns to baseline or was slightly reduced at 3 to 12 months after donation, particularly for fatigue. A surgical procedure is a stress factor for patients and the impact on their physical condition can reduce quality of life. The physical condition of a patient is a predictive factor for postoperative outcomes. Improving the physical activity of the donor prior to surgery by means of a prehabilitation programme may lead to improve physical condition during surgery and faster recovery postoperatively. Our key objective is to evaluate the impact of a preoperative supervised training programme on fatigue scores postoperatively.

Subtheme 4: The role of bariatric surgery in kidney transplantation

Project leader: R.C. Minnee

Project description: Obesity is becoming a major challenge in developed countries and is likewise affecting the population of patients either awaiting or recipients of a kidney transplantation. Obesity is associated with a multitude of concomitant health problems, such as metabolic syndrome and cardiovascular diseases, therefore linked to inferior transplant outcome. Bariatric surgery is an established treatment of morbid obesity. Our two key objectives are: (I) to evaluate the impact of bariatric surgery on graft survival of kidney transplant recipients; (II) to analyze which treatment strategy provides the best outcome: bariatric surgery before or after kidney transplantation.

Subtheme 5: Tumor immunopathology

Project leader: prof. dr. C.H.J. van Eijck

Project description: Tumor immunopathology laboratory hosts a multidisciplinary team of basic, translational, and clinical researchers focusing on studying two of the most complicated types of cancers: Brain Tumors, Lung and Pancreatic Cancers. It integrates national and international scientists and students to answer questions fundamental to our understanding of brain metastasis and pancreatic cancer. We identify circulating biomarkers for early diagnosis and to monitor and control the progression of pancreatic cancer. We identify new genes/proteins/pathways involved in the two diseases. In our laboratory, we use various state-of-the-art techniques that enable reaching our goal. We use liquid- and solid biopsies and biospecimens including fresh frozen and formalin-fixed paraffin-embedded tumor tissue. We perform a comprehensive range of techniques including DNA- and RNA sequencing, targeted gene expression, microRNA, ctDNA, immune profiling and mass spectrometry proteomics to monitor the effect of therapy in pancreatic cancer patients. An important part of our research is focusing on identifying neoantigens of pancreatic cancer in order to open new therapeutic opportunities. In addition, we utilize various organ models (organ-on-a chip) in order to study our discoveries at the functional level.

Our team collaborates with international laboratories to create novel genomics techniques that give new insights about the clonal heterogeneity of pancreatic tumors and find new ways to overcome drug resistance. We also collaborate with international groups to use the genetically engineered pancreatic cancer mouse model. In addition, we collaborate with bioinformatics teams to help identifying new mutations in pancreatic cancers. We are in a process of developing software that will enable the clinicians from all over the world to reach a precise diagnosis of the disease. We collaborate with immunologist to unravel various aspects of the immune response involved in the development, maintenance and resolution of pancreatic cancer.

The tumor immunopathology laboratory is located in the department of Pathology at Erasmus Medical Center, Rotterdam. It is greatly supported by “Support Casper” foundation, and it is part of the Oncolytic Viro-Immuno Therapy (OVIT) consortium.

We are looking for medical or biomedical master students for a period of at least 6 months. The candidates will spend most of their time conducting original research and writing scientific papers In addition, they could follow courses relevant to the research and obtain credits under the European Credit Transfer System (ECTS). The master student will be supervised by a full academic professor and supported by senior scientists. English language and basic knowledge of the techniques mentioned above is recommended but not necessary.

Theme 8: Atherosclerosis as a predictor for outcome after PTA / Stenting: A retrospective analysis of abdominal CT-scans.

Prof. dr. H.J.M. Verhagen

Background:

In patients with occlusive or stenotic arterial disease, treatment is necessary when Fontaine stage III/IV, i.e. critical ischemia, is reached. Initially the treatment of choice is PTA, or percutaneous transluminal angioplasty, with or without stenting.

Occlusive or stenotic arterial disease often occurs in the iliac trajectory and is caused by atherosclerosis. It is a slowly progressive, systemic, disease that causes massive arterial damage before it becomes clinically manifest. This is illustrated by the large quantity and volume of the calcifications in the atherosclerotic plaques.

The major complication of PTA with or without stenting is recurrence, which requires another PTA with stenting. When this is insufficient a bypass operation is necessary. The period between the initial complaints of the patient and the bypass is substantial since one or more PTA procedures with or without stenting are performed.

The influence of the atherosclerotic load on recurrence after PTA/stenting is unknown. However, the thought of higher recurrence rates in patients with higher atherosclerotic loads is conceivable and perhaps these patients should receive a bypass directly instead of multiple PTA’s.

To date, the atherosclerotic load can be determined by means of calcium scoring on CT-scan. The radio-opaque atherosclerotic lesions can be quantified with specific calcium scoring software, which expresses the atherosclerotic calcifications in Agatson-score, calcium mass and —volume. Multiple studies show the Agatson-score to be a predictor for congestive heart failure.

The aim of this research project is to study the potential of the calcium score in the iliac trajectory as a predictor for the long term outcome of PTA and stenting and to determine whether it is possible to distinguish patients that will be better off with a bypass.

Theme 9: ‘Molecular imaging of aneurysms’

Prof. dr. H.J.M. Verhagen

Molecular imaging is an important new technology in translational medicine. For this project, we aim at molecular imaging of protease activity of MMPs/cathepsins upregulated during aneurysm formation, using protease-activatable near-infrared fluorescence (NIRF) probes, so-called smart optical probes. These protease-activatable sensors directly report the in vivo/ex-vivo activity of the key biomarkers in aneurysm, providing information complementary to immunolocalization in tissue sections. We will test smart-optical NIRF probes specific for MMPs in tissue sections from patients and aneurysm mouse models.

To obtain a more holistic view on the proteome changes occurring during aneurysm formation, we plan to follow a proteomic approach. We will start with candidate-based proteomics on tissue sections from patients and analyze several candidate proteins. Furthermore, we will compare protease activity of a variety of proteases (such as MMP8 and Cathepsins) by immunohistochemical and biochemical analysis among patient material, and established models for thoraceous and abdominal aortic aneurysm. A full un-biased proteomic screen will be performed using 2D gel based DIGE. 2D-DIGE uses differential labeling of protein samples by Cy-dyes enabling detection and quantitation of two different protein samples in a single 2D-gel. Changes in the protein expression of the samples of the aneurysm mice will then be identified using state-of-the-art mass spectrometric techniques (such as MALDI-TOF/TOF and LC-MS/MS). An important goal of the proteome analysis of Fibulin-4 mouse models is to obtain a lead for development of optical probes for molecular imaging of aneurysms and medical therapy. This project will yield smart optical probes that detect aneurysms in human tissue material, which will be invaluable for future medicine and image-guided surgery.

Theme 10: Project: Inflammation response during surgery and postoperative outcome in vascular patients.

Drs. O. Schouten

Background: Postoperative cardiac events are the major cause of morbidity and mortality in vascular surgery patients. Cardiac events are related to the presence and extend of coronary artery disease. Coronary inflammation, leading to coronary plaque rupture and thrombosis plays an important role. Coronary plaque rupture can lead to myocardial infarction and cardiac arrhythmias.

Aim: To assess the relation between inflammation responses during surgery, assessed in blood and tissue and postoperative cardiac outcome.

Methods: 50 consecutive vascular surgery patients will be enrolled over 9 months. In all patients, cardiac risk factors, quality of life assessment, inflammations markers and ECG will be assessed prior to surgery. During surgery repeated inflammation markers in blood and tissue are collected. After surgery patients are screened for late cardiac events. Inflammation markers determined in blood and tissue are interleukin-6 and high-sensitive c-reactive protein.

Expected results: Inflammation response during surgery can predict postoperative cardiac outcome, irrespective of inflammation complications.

Task of student: to be involved in perioperative care, including outpatient clinic, surgery, postoperative care at the ward. The results will be presented as an abstract for a scientific session and manuscript.

Theme 11: Prognostic/Predictive Factors and Treatment Outcome in TNF-based Isolated Limb Perfusion (ILP) for Irresectable tumors of the Extremities

Dr. Cornelis Verhoef, Prof. dr. Alexander M.M. Eggermont

The Department of Surgical Oncology of the Erasmus MC-Daniel den Hoed Cancer Center has the largest experience world-wide in an ILP-based limb salvage program for irresectable extremity tumors. Rotterdam-coordinated multicenter trials utilizing Tumor Necrosis Factor-alpha lead to the approval of ILP with TNF in combination with melphalan by the EMEA as the limb salvage treatment modality for irresectable extremity tumors. Hereafter 40 European Cancer Centers were trained at the ErasmusMC-Daniel den Hoed to conduct TNF-based ILP and were activated and accredited all over Europe. The prospective Rotterdam Data Base defines over 40 patient, tumor and perfusion characteristics and is the cornerstone to define prognostic and predictive factors for treatment outcome.

With > 400 ILPs for irresectable soft tissue sarcomas and > 200 ILPs for patients with multiple in transit metastases, as well as ILPs for a variety of rare tumors or rare limb-threatening conditions, it is unique in size and quality. This size allows to refine questions with respect to different histologies in soft tissue sarcomas (outcome by grade 1-2-3, outcome by the about 20 different histologic types, borderline malignancies, aggressive fibromatosis, desmoid tumors etc.) and outcome, tumor site characteristics and outcome (for instance proximal vs distal tumors; upper vs lower extremity tumors).

The ‘Rotterdam-Prospective Database’ provides a rare opportunity to study, define and hence tailer treatment options to patients with limb-threatening extremity tumors.

Theme 12: Prognostic Factors in Sentinel Node Positive Melanoma Patients: The Rotterdam Criteria for Tumor Load

Drs. Alexander C.J. van Akkooi, Prof. dr. Alexander M.M. Eggermont

In Rotterdam we have gathered the largest SN-tumor load reclassified database of Sentinel Node (SN) positive melanoma patients in the world (n=1000). This data base will be expanded over the next year to about 1500 cases. This project has been conducted within the framework of the European Organization for Research and Treatment of Cancer (EORTC). It includes large centers from the U.K., France, Germany, Poland, Italy and the Netherlands.

Previous studies from our group have demonstrated that patients with minimal SN tumor burden have a significantly better prognosis, equal to SN negative patients and might not require a lymph node dissection. The regional relapse rate in these patients is virtually none, identical to SN negative patients. However, the exact value of these small dormant metastases is not yet certain. When taking SN tumor burden into consideration as a false positive result of SN staging, there does not seem to be a survival benefit for performing this staging procedure when compared to lymph node dissection in case of palpable nodal relapses.

Further research is needed, with an increased study power to further analyze the prognostic value and possible treatment implications of minimal SN tumor burden. For this purpose slides will need to be reviewed from all participating centers. A case-controlled study with SN negative patients will also be conducted.

The student will be trained to analyze SN tumor burden on pathological material, will update and analyze the database with help of a statistician, will have the possibility to visit EORTC centers. Combinations with other study projects and clinical internships are also possible. Several publications are foreseen which guarantees co-authorships. Minimally 1 publication as first author will be guaranteed.

Theme 13: Prevalence, severity and impact of gastrointestinal symptoms after oesophagectomy for cancer

Dr. B.P.L. Wijnhoven

The incidence of oesophageal cancer is rising in the Netherlands. Resection of the oesophagus (oesophagectomy) is the corner stone in the treatment of this highly aggressive disease and offers the best chance for long term survival. However, 50-60% of patients after oesophagectomy will develop a loco-regional recurrence and/or distant metastases and ultimately succumb.

Oesophagectomy is a highly invasive surgical procedure. Via a thoracic or abdominal route the oesophagus is resected and continuity of the gastrointestinal tract restored with the stomach: a so called gastric tube. Hence, intake, transportation and digestion of food will change and is restricted in most patients. Moreover, approximately 50% of patients after oesophagectomy develop a stricture of the anastomosis between the remnant oesophagus in the neck and the gastric conduit resulting in troublesome dysphagia. The occurrence of bile and acid reflux, nausea and diarrhoea are also well known debilitating symptoms after oesophagectomy. Surprisingly, not many studies are known that have looked at these gastrointestinal symptoms after oesophagectomy and its impact on the patients quality of life. Also the permanent fear of recurrence of the disease together with a decreased fysical fittness, has an enormous impact on patients’ quality of life already.

The aim of this research project is to determine the prevalence, severity and impact of gastrointestinal symptoms in a large cohort of patients before and after oesophagectomy for cancer. Hoe many patients report symptoms after oesophagectomy? Does it have an impact on their daily living? Is there any effective treatment? Published and new designed symptom- and quality of life questionnaires will be used to answer these questions.

The department of surgery at the Erasmus MC has a national and international reputation on the treatment of oesophageal cancer patients. About 80 patients undergo oesophagectomy for cancer on an annual basis. Close collaboration with the departments of gastroenterology and medical oncology will be sought.

It is expected that the results will be presented at a scientific meeting and that a manuscript constructed for publication in an international journal.

Theme 14: Radiation induced soft tissue sarcoma (RISTS)

Dr. A.N. van Geel

Four out of 100 patients with a soft tissue sarcoma have a history of previous radiation therapy in the same area. Most initial cancers were breast cancer and lymphomas. RISTS are frequently high grade sarcomas and the treatment options are restricted because subsequent radiotherapy after resection is not feasible anymore. The prognosis is poor.

Data in the literature are very limited and the series are small. The purpose of this study is to define the risk of RISTS in cancer patients and to identify clinical and pathological risk factors for prognosis. The study is intended to be a nationwide study in all centers with a radiation department in collaboration with the department of pathology and radiotherapy. A similar study was started a few years ago, but failed. Retrieving the data showed to be very time consuming. It is expected this study will be the largest study in RISTS.

Theme 15: Efficacy of RFA in the treatment of liver tumors

Prof. dr. J.N.M. IJzermans (Hepatobiliair surgery)

Introduction: Benign as well as malignant liver tumors may be treated by surgical resection. The Department of Surgery of the Erasmus MC has one of the largest hepatobiliary programs in the Netherlands and up to 100 patients are being treated by a liver resection each year. Although the surgical techniques and the peri-operative care have improved significantly in the last decade a liver resection still has a large impact on the quality of life of a patient. Alternative treatment modalities are being developed and one of these is radiofrequent ablation. By using this technique a 17 gauge needle is being introduced into the tumor and via this route a current is released in the centre of the lesion leading to a temperature increase and ablation of the surrounding tissue. The treatment can be conducted with a low morbidity and with a short hospital stay.

However, it remains to be determined whether this treatment may compete with the golden standard of liver surgery. The candidate will design a cost-effectiveness study and with the availability of data from the Erasmus MC liver tumor database he/she will determine the criteria for the use of RFA. The candidate will work together with the liver surgeons and intervention radiologists to collect more data on the RFA treatment and the surgical resections. He/she will write a manuscript and present the work to expert meetings.

Theme 16: Hepatocellular adenoma

Prof. dr. J.N.M. IJzermans, surgeon, Dr. T. Terkivatan, surgeon

Study Design: Hepatocellular adenoma is a benign liver tumor that most often occurs in young female patients and is associated with the use of oral contraceptives.

The most optimal treatment in case of an asymptomatic hepatocellular adenoma still remains to be determined. Due to the low incidence of this tumor no large series have been reported and management depends heavily on small retrospective studies or case-reports.

Despite the fact that we are dealing with a benign tumor, the small risk of bleeding and the very rare cases of malignant degeneration tend to be the most important reasons to perform a surgical resection, even in case of small tumors. Such an approach is inevitably associated with morbidity and mortality rates.

In our Centre we already treated many of this patients by surgery and some of them with a percutaneous thermal ablation technique, the radiofrequency ablation (RFA). Furthermore, some patients are followed by radiological means, showing that regression of the tumor occurs in a significant number of patients after they have stopped the use of oral contraceptives. It is interesting to collect all data from these patients to be informed about the natural course when a conservative approach is being followed and the outcomes of different kind of interventional of surgical therapies. This will lead to a more evidence-based approach in the management of this benign lesion and may be a first step towards the organization of a multinational database leading eventually to the most optimal management strategy of hepatocellular adenomas.

The student will perform an update of a data file with all patients having a hepatocellular adenoma who were seen in our clinic between 1975 en 2007, and he or she will be enabled to write a manuscript on this research. Besides a prospective data-base will be organized for institutional and (inter)national use.